Calcium antagonists and beta-blockers: impact on cardiovascular and cerebrovascular events

It is well established that elevated blood pressure is a major risk factor for cardiovascular and cerebrovascular events, and that controlling hypertension reduces these risks. Although most classes of antihypertensive agents play a role in risk reduction, none offers blanket reductions for all adverse events. The beta-blockers, while the agents of choice for those with ischemic heart disease and for disease states requiring reducing heart rate, are inappropriate first-line therapies in patients whose primary concern is stroke risk reduction. In patients who require heart rate-lowering therapy but who cannot tolerate beta-blockers, long-acting nondihydropyridine calcium antagonists offer the benefits of heart rate reduction, as well as the vasodilation that is characteristic of the calcium antagonists as a class. This article reviews the data on risk reduction involving the beta-blockers and calcium antagonists, as well as other antihypertensive classes that have been shown to reduce the risk of cerebrovascular and cardiovascular disease.     

Metabolic effects of carvedilol vs metoprolol in patients with type 2 diabetes mellitus and hypertension: a randomized controlled trial

Context  -Blockers have been shown to decrease cardiovascular risk in patients with hypertension and type 2 diabetes mellitus (DM); however, some components of the metabolic syndrome are worsened by some -blockers. Objective  To compare the effects of -blockers with different pharmacological profiles on glycemic and metabolic control in participants with DM and hypertension receiving renin-angiotensin system (RAS) blockade, in the context of cardiovascular risk factors. Design, Setting, and Participants  A randomized, double-blind, parallel-group trial (The Glycemic Effects in Diabetes Mellitus: Carvedilol-Metoprolol Comparison in Hypertensives [GEMINI]) conducted between June 1, 2001, and April 6, 2004, at 205 US sites that compared the effects of carvedilol and metoprolol tartrate on glycemic control. The 1235 participants were aged 36 to 85 years with hypertension (>130/80 mm Hg) and type 2 DM (glycosylated hemoglobin [HbA_1c], 6.5%-8.5%) and were receiving RAS blockers. Participants were followed up for 35 weeks. Interventions  Participants were randomized to receive a 6.25- to 25-mg dose of carvedilol (n = 498) or 50- to 200-mg dose of metoprolol tartrate (n = 737), each twice daily. Open-label hydrochlorothiazide and a dihydropyridine calcium antagonist were added, if needed, to achieve blood pressure target. Main Outcome Measures  Difference between groups in mean change from baseline HbA_1c following 5 months of maintenance therapy. Additional prespecified comparisons included change from baseline HbA_1c in individual treatment groups, treatment effect on insulin sensitivity, and microalbuminuria. Results  The 2 groups differed in mean change in HbA_1c from baseline (0.13%; 95% confidence interval [CI], –0.22% to –0.04%; P = .004; modified intention-to-treat analysis). The mean (SD) HbA_1c increased with metoprolol (0.15% [0.04%]; P<.001) but not carvedilol (0.02% [0.04%]; P = .65). Insulin sensitivity improved with carvedilol (–9.1%; P = .004) but not metoprolol (–2.0%; P = .48); the between-group difference was –7.2% (95% CI, –13.8% to –0.2%; P = .004). Blood pressure was similar between groups. Progression to microalbuminuria was less frequent with carvedilol than with metoprolol (6.4% vs 10.3%; odds ratio, 0.60; 95% CI, 0.36-0.97; P = .04). Conclusions  Both -blockers were well tolerated; use of carvedilol in the presence of RAS blockade did not affect glycemic control and improved some components of the metabolic syndrome relative to metoprolol in participants with DM and hypertension. The effects of the 2 -blockers on clinical outcomes need to be compared in long-term clinical trials.      

Once-daily treatment of patients with hypertension: a placebo-controlled study of amlodipine and benazepril vs amlodipine or benazepril alone

OBJECTIVE: To compare the efficacy, tolerability, and safety of once-daily therapy with amlodipine 5 mg/benazepril 10 mg vs amlodipine 5 mg, benazepril 10 mg, and placebo. DESIGN: Randomised, double-blind, placebo-controlled, parallel-group, multicentre trial. SETTING: Twenty-two clinical centres, including private practice groups and academic research clinics.Patients: A total of 530 patients between 21 and 80 years of age with essential hypertension were screened for the study, and 454 were randomised to treatment with amlodipine 5 mg/benazepril 10 mg, amlodipine 5 mg, benazepril 10 mg, or placebo for 8 weeks. RESULTS: Amlodipine 5 mg/benazepril 10 mg produced greater reductions from baseline in sitting diastolic blood pressure than amlodipine 5 mg (P < 0.03), benazepril 10 mg (P < 0.001), and placebo (P < 0.001). The response rate in the amlodipine 5-mg/benazepril 10-mg treatment group (66.4%) was better than that observed in the amlodipine 5-mg (50.0% P < 0.02), benazepril 10-mg (38.3% P < 0.001), and placebo (24.4% P < 0.001) groups. There was no significant difference in heart rate among the four groups. The incidence of oedema in the amlodipine 5-mg/benazepril 10-mg (1.7%) group was somewhat less than that in the amlodipine 5-mg (4.5%) group. CONCLUSIONS: Therapy with amlodipine 5 mg/benazepril 10 mg was well tolerated and was superior to amlodipine 5 mg, benazepril 10 mg, and placebo in reducing sitting diastolic blood pressure in patients with essential hypertension.     

Antihypertensive therapy in the elderly

Recent studies have documented that arterial hypertension increases cardiovascular morbidity and mortality even in the geriatric population. Some elderly hypertensive patients, like younger patients, can benefit from antihypertensive therapy. Antihypertensive therapy should be carefully adjusted to suit the cardiovascular pathophysiology of elderly patients.     

Left atrial abnormalities indicating diastolic ventricular dysfunction in cardiopathy of obesity

Electrocardiograms and M-mode echocardiograms were evaluated in lean and obese patients, either normotensive or hypertensive, who were paired for mean arterial pressure, age, and sex. Electrocardiographic evidence of left atrial abnormalities (LAA) occurred more frequently (p less than 0.01) and left atrial size was greater in the obese than in the lean patients (p less than 0.01). The left atrial emptying index, an indicator of early diastolic ventricular function, was reduced in obese patients (p less than 0.01), most markedly in those with obesity-hypertension. The left atrial emptying index was reduced in obese patients with electrocardiographic LAA compared to obese patients without this electrocardiographic sign (p less than 0.02). A close correlation (r = 0.61, p less than 0.001) was obtained between the left atrial emptying index and atrial ECG abnormalities. These left atrial abnormalities in obesity and particularly in obesity-hypertension indicate diastolic ventricular dysfunction.     

Renal involvement follows cardiac enlargement in essential hypertension

To assess the relationship between early clinically detectable involvement of hypertensive vascular disease in heart and kidneys, we obtained systemic and renal hemodynamic and M-mode echocardiographic measurements in 65 patients with essential hypertension. The results indicate that patients with and without left ventricular hypertrophy had similar renal hemodynamic findings. In contrast, patients with altered renal hemodynamic measurements (ie, reduced renal distribution of cardiac output and, therefore, absolute renal blood flow with increased renal vascular resistance) and increased serum uric acid levels also had increased left ventricular posterior and septal wall thicknesses and mass index. Moreover, these data also demonstrated that in patients with altered renal hemodynamics, the lower the renal distribution of cardiac output and the higher the serum uric acid levels, the greater were the indexes of cardiac enlargement. These results demonstrated that the pathophysiological and hemodynamic effects of essential hypertension in the heart precede those in the kidneys.